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Wei Liang, Kang Li, Haiyou Gao, Kunming Li, Jiansong Zhang, Qian Zhang, Xinying Jiao, Jialong Yang, Xiumei Wei. Full T-cell activation and function in teleosts require collaboration of first and co-stimulatory signals. Zoological Research, 2024, 45(1): 13-24. doi: 10.24272/j.issn.2095-8137.2023.053
Citation: Wei Liang, Kang Li, Haiyou Gao, Kunming Li, Jiansong Zhang, Qian Zhang, Xinying Jiao, Jialong Yang, Xiumei Wei. Full T-cell activation and function in teleosts require collaboration of first and co-stimulatory signals. Zoological Research, 2024, 45(1): 13-24. doi: 10.24272/j.issn.2095-8137.2023.053

Full T-cell activation and function in teleosts require collaboration of first and co-stimulatory signals

doi: 10.24272/j.issn.2095-8137.2023.053
Supplementary data to this article can be found online.
The authors declare that they have no competing interests.
W.L. designed and performed the experiments, analyzed the data, and drafted the manuscript. Kang L., H.G., Kunming L., J.Z., Q.Z., and X.J. performed the experiments. J.Y. and X.W. acquired funding, conceived the project, designed the experiments, analyzed the data, and drafted the manuscript. All authors read and approved the final version of the manuscript.
#Authors contributed equally to this work
Funds:  This study was supported by the National Key Research and Development Program (2022YFD2400804), National Natural Science Foundation of China (32022086, 31972822), and Natural Science Foundation of Shanghai (20ZR1417500)
More Information
  • Mammalian T-cell responses require synergism between the first signal and co-stimulatory signal. However, whether and how dual signaling regulates the T-cell response in early vertebrates remains unknown. In the present study, we discovered that the Nile tilapia (Oreochromis niloticus) encodes key components of the LAT signalosome, namely, LAT, ITK, GRB2, VAV1, SLP-76, GADS, and PLC-γ1. These components are evolutionarily conserved, and CD3ε mAb-induced T-cell activation markedly increased their expression. Additionally, at least ITK, GRB2, and VAV1 were found to interact with LAT for signalosome formation. Downstream of the first signal, the NF-κB, MAPK/ERK, and PI3K-AKT pathways were activated upon CD3ε mAb stimulation. Furthermore, treatment of lymphocytes with CD28 mAbs triggered the AKT-mTORC1 pathway downstream of the co-stimulatory signal. Combined CD3ε and CD28 mAb stimulation enhanced ERK1/2 and S6 phosphorylation and elevated NFAT1, c-Fos, IL-2, CD122, and CD44 expression, thereby signifying T-cell activation. Moreover, rather than relying on the first or co-stimulatory signal alone, both signals were required for T-cell proliferation. Full T-cell activation was accompanied by marked apoptosis and cytotoxic responses. These findings suggest that tilapia relies on dual signaling to maintain an optimal T-cell response, providing a novel perspective for understanding the evolution of the adaptive immune system.
  • Supplementary data to this article can be found online.
    The authors declare that they have no competing interests.
    W.L. designed and performed the experiments, analyzed the data, and drafted the manuscript. Kang L., H.G., Kunming L., J.Z., Q.Z., and X.J. performed the experiments. J.Y. and X.W. acquired funding, conceived the project, designed the experiments, analyzed the data, and drafted the manuscript. All authors read and approved the final version of the manuscript.
    #Authors contributed equally to this work
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